{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T05:44:39Z","timestamp":1772257479764,"version":"3.50.1"},"reference-count":61,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2020,5,16]],"date-time":"2020-05-16T00:00:00Z","timestamp":1589587200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia","award":["PTDC\/CVT-REP\/4202\/2014"],"award-info":[{"award-number":["PTDC\/CVT-REP\/4202\/2014"]}]},{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia","award":["UIDP\/CVT\/00276\/2019"],"award-info":[{"award-number":["UIDP\/CVT\/00276\/2019"]}]},{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia","award":["SFRH\/BD\/101058\/2014"],"award-info":[{"award-number":["SFRH\/BD\/101058\/2014"]}]},{"name":"NAWA, Poland and Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia, Portugal","award":["No. PPN\/BIL\/2018\/1\/00250\/U\/0001"],"award-info":[{"award-number":["No. PPN\/BIL\/2018\/1\/00250\/U\/0001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Animals"],"abstract":"<jats:p>Neutrophil extracellular traps (NETs) fight endometritis, and elastase (ELA), a protease found in NETs, might induce collagen type I (COL1) accumulation in equine endometrium. Metallopeptidases (MMPs) are involved in extracellular matrix balance. The aim was to evaluate the effects of ELA and sivelestat (selective elastase inhibitor) on MMP-2 and MMP-9 expression and gelatinolytic activity, as well as the potential inhibitory effect of sivelestat on ELA-induced COL1 in equine endometrium. Endometrial explants from follicular (FP) and mid-luteal (MLP) phases were treated for 24 or 48 h with ELA, sivelestat, and their combination. Transcripts of COL1A2, MMP2, and MMP9 were evaluated by qPCR; COL1 protein relative abundance by Western blot, and MMP-2 and MMP-9 gelatinolytic activity by zymography. In response to ELA treatment, there was an increase in MMP2 mRNA transcription (24 h) in active MMP-2 (48 h), both in FP, and in MMP9 transcripts in FP (48 h) and MLP (24 h) (p &lt; 0.05). Sivelestat inhibited ELA-induced COL1A2 transcripts in FP (24 h) and MLP (24 h, 48 h) (p &lt; 0.05). The sivelestat inhibitory effect was detected in MMP9 transcripts in FP at 48 h (p &lt; 0.05), but proteases activity was unchanged. Thus, MMP-2 and MMP-9 might be implicated in endometrium fibrotic response to ELA. In mare endometrium, sivelestat may decrease ELA-induced COL1 deposition and hinder endometrosis development.<\/jats:p>","DOI":"10.3390\/ani10050863","type":"journal-article","created":{"date-parts":[[2020,5,18]],"date-time":"2020-05-18T02:43:42Z","timestamp":1589769822000},"page":"863","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["The In Vitro Inhibitory Effect of Sivelestat on Elastase Induced Collagen and Metallopeptidase Expression in Equine Endometrium"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0075-262X","authenticated-orcid":false,"given":"Ana","family":"Amaral","sequence":"first","affiliation":[{"name":"CIISA\u2014Centre for Interdisciplinary Research in Animal Health, Faculty of Veterinary Medicine, University of Lisbon, 1300-477 Lisbon, Portugal"}]},{"given":"Carina","family":"Fernandes","sequence":"additional","affiliation":[{"name":"CIISA\u2014Centre for Interdisciplinary Research in Animal Health, Faculty of Veterinary Medicine, University of Lisbon, 1300-477 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4389-445X","authenticated-orcid":false,"given":"Maria Rosa","family":"Rebord\u00e3o","sequence":"additional","affiliation":[{"name":"CIISA\u2014Centre for Interdisciplinary Research in Animal Health, Faculty of Veterinary Medicine, University of Lisbon, 1300-477 Lisbon, Portugal"},{"name":"Coimbra College of Agriculture, Polytechnic Institute of Coimbra, 3045-601 Coimbra, Portugal"}]},{"given":"Anna","family":"Sz\u00f3stek-Mioduchowska","sequence":"additional","affiliation":[{"name":"Institute of Animal Reproduction and Food Research, Polish Academy of Science,10-748 Olsztyn, Poland"}]},{"given":"Karolina","family":"Lukasik","sequence":"additional","affiliation":[{"name":"Institute of Animal Reproduction and Food Research, Polish Academy of Science,10-748 Olsztyn, Poland"}]},{"given":"Barbara","family":"Gawronska-Kozak","sequence":"additional","affiliation":[{"name":"Institute of Animal Reproduction and Food Research, Polish Academy of Science,10-748 Olsztyn, Poland"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3894-3488","authenticated-orcid":false,"given":"Lu\u00eds","family":"Telo da Gama","sequence":"additional","affiliation":[{"name":"CIISA\u2014Centre for Interdisciplinary Research in Animal Health, Faculty of Veterinary Medicine, University of Lisbon, 1300-477 Lisbon, Portugal"}]},{"given":"Dariusz J.","family":"Skarzynski","sequence":"additional","affiliation":[{"name":"Institute of Animal Reproduction and Food Research, Polish Academy of Science,10-748 Olsztyn, Poland"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0622-6513","authenticated-orcid":false,"given":"Gra\u00e7a","family":"Ferreira-Dias","sequence":"additional","affiliation":[{"name":"CIISA\u2014Centre for Interdisciplinary Research in Animal Health, Faculty of Veterinary Medicine, University of Lisbon, 1300-477 Lisbon, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2020,5,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1016\/0093-691X(94)90173-G","article-title":"Sperm-induced leukocytosis in the equine uterus","volume":"41","author":"Kotilainen","year":"1994","journal-title":"Theriogenology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1093\/biolreprod\/52.monograph_series1.515","article-title":"Onset and Duration of Uterine Inflammatory Response of Mares after Insemination with Fresh Semen","volume":"52","author":"Katila","year":"1995","journal-title":"Boil. 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